Redesigning Clinical Trials Flashcards
The most important document in any clinical trial?
Informed consent form (ICF) and patient information sheet
Elements of informed consent?
- Description of the investigation
- Risks & discomforts
- Benefits
- Confidentiality: participants and their info. kept private
- In the event of injury, what to do & who to contact
- Contacts: staff of medical centre, a contact name & phone no. in the research team for problems
- Voluntary Participation Statement
ICF must comply with
- Principles of Nuremberg Code
- The Declaration of Helsinki
- The Belmont Report
Consenting as a process
- Patient identified
- Phone call to introduce the trial
- Shown the consent sheet
- Changes may be made - trials extended; staff changed → participants will need to re-consent
Issues with ICF
- Document is often really long
- Sometimes templated by institution
- High Stakes Trials length can be 30-40 pages - in certain places, ICFs have to be 10 pages or less - These documents are sometimes written with no patient interaction at all
- Fear of litigation might lead regulatory bodies to demand legally precise jargon
- Patient understanding is inversely proportional to the page count of the ICF
Why use AI tools when designing clinical trials?
To organise clinical data to develop and select criteria
Incentives to enhance recruitment for clinical trials
→ Incentives can also take many forms, including:
- Cash or cash-like rewards (money, vouchers, reimbursement for expenses/ time/ uncomfortable procedures, additional resources for recruiters, etc.)
- Providing drug and physician care for free - Social, emotional, or tokenistic rewards (gifts, donation to charity)
- Reputational incentives, praise, social recognition (such as authorship on research papers), and public reporting
Benefits of remote or hybrid trials
- Eliminating travel for patients
- COVID-compliance
- Reduced dropout
- Flexible
- Patient-first approach
Importance of logistics in hybrid approach with regard to remote appointments
- Ensuring patients receive things with no delay
- Medically trained couriers required to deliver things safely, legally
- Means managing higher volumes of patient data
- User research required to ensure compliance is as easy as possible
How were clinical trials for COVID vaccines different from the standard clinical trial procedure for a vaccine?
FDA and other authorities allowed Phases I, II, and III to run in parallel by removing the financial risk, allowing them to gamble on options that might not have been effective
Traditionally, trials do ‘age de-escalation.’ What does this mean?
Start with healthy adults, then do older people and children
Examples of trials that need a new design structure and why
- NTF trials: elderly blinded where they didn’t need to be - placebo effects are only short term, sham surgery deemed unethical
- Oncology trials - patients excluded if had prior chemotherapy, advanced stages of disease, not newly diagnosed - eliminating a lot of the people who will need the treatment
Umbrella vs basket trials in oncology
Umbrella: multiple drugs tested against multiple genetic mutations within a single cancer type
vs
Basket: a handful (typically 1 or 2) of drugs tested against a handful of genetic mutations across multiple cancer types
Antibody vs small molecule
Antibodies: highly selective but specific to cell surface, must be delivered intravenously or subcutaneously
Small molecules: quite selective, also smaller than antibodies, not limited to cell surface
the HUDSON trial
- Phase II study on advanced non small cell lung cancer (NSCLC)
- Patients who had progressed on prior anti-PDL1 therapy
- PDL1 binds to a checkpoint receptor on immune cells
- Cancer cells produce PDL1 to avoid immune response - anti-PDL1 prevents this
- Umbrella Study of 9 immunotherapy combinations with Durvalumab
- Recruitment based on biomarkers
- Use of peripheral blood samples, including finding ctDNA (works better than CT scans/PET imaging)
- Detect, characterise, monitor cancer
